Anti-tumor efficacy of fulvestrant in estrogen receptor positive gastric cancer

To investigate the prognostic role of the estrogen receptor (ER) in gastric cancer (GC) patients, tumor tissues from 932 patients with advanced GC were assessed for ER expression using immunohistochemistry and their clinicopathologic features were evaluated. Forty patients (4.3%) had ER expression a...

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Bibliographic Details
Published in:Scientific reports 2014-12, Vol.4 (1), p.7592, Article 7592
Main Authors: Yi, Jun Ho, Do, In-Gu, Jang, Jiryeon, Kim, Seung Tae, Kim, Kyoung-Mee, Park, Se Hoon, Park, Joon Oh, Park, Young Suk, Lim, Ho Yeong, Kang, Won Ki, Lee, Jeeyun
Format: Article
Language:English
Subjects:
13/51
13/89
17β-Estradiol
631/67/1504/1829
631/67/1857
82/80
Adult
Aged
Antineoplastic Agents, Hormonal - pharmacology
Antineoplastic Agents, Phytogenic - pharmacology
Breast cancer
Carcinogenesis
Cell Line, Tumor
Cell proliferation
Disease-Free Survival
E-cadherin
Estradiol - analogs & derivatives
Estradiol - pharmacology
Estrogen receptors
Estrogens
Female
Fulvestrant
Gastric cancer
Gene Expression Regulation, Neoplastic - drug effects
Humanities and Social Sciences
Humans
Immunohistochemistry
Male
Middle Aged
multidisciplinary
Paclitaxel
Paclitaxel - pharmacology
Receptors, Estrogen - biosynthesis
Science
siRNA
Stomach Neoplasms - drug therapy
Stomach Neoplasms - metabolism
Stomach Neoplasms - mortality
Stomach Neoplasms - pathology
Survival Rate
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Summary:To investigate the prognostic role of the estrogen receptor (ER) in gastric cancer (GC) patients, tumor tissues from 932 patients with advanced GC were assessed for ER expression using immunohistochemistry and their clinicopathologic features were evaluated. Forty patients (4.3%) had ER expression and they were more frequently associated with diffuse type gastric cancer and shorter disease free survival. Furthermore, we carried out in vitro analysis to evaluate the effect of ER modulation on the proliferation of GC cell lines. Estradiol enhanced proliferation of ER positive GC cells while it did not show any effect on ER negative GC cells. When ER was inhibited by fulvestrant and ER siRNA, estradiol-induced proliferation of ER positive GC cell was suppressed. Paclitaxel showed synergistic anti-proliferative impacts with fulvestrant. Suppressing ER by fulvestrant, paclitaxel and ER siRNA showed increased expression of E-cadherin, which is a crucial factor in diffuse-type carcinogenesis.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep07592